POS1462 IMMUNOEMATHOLOGIC FEATURES IN A COHORT OF PEDIATRIC PATIENTS WITH SJÖGREN’S SYNDROME: AN OVERLAP WITH AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME (ALPS)-LIKE DISORDERS
Authors: S. Ancona, C. Morreale, M. DI Filippo, G. Simiele, C. Lavarello, C. Malattia
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Childhood Sjögren's syndrome (cSS) is a chronic autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands leading to their dysfunction [1]. Even though recurrent parotitis and sicca symptoms seems to be the most frequently reported features, cSS could have a wide range of clinical and laboratory manifestations such as autoimmune cytopenia, hypergammaglobulinemia, lymphadenopathy, fever and arthralgia [2]. These manifestations can also be seen in patients with autoimmune lymphoproliferative syndrome (ALPS). ALPS is a rare hematologic disorder characterized by an altered lymphocyte homeostasis due to a defective apoptotic mechanism [3]. In addition, cSS and ALPS are significantly associated with increased risk of lymphoid malignancy, most commonly non-Hodgkin lymphoma. <h3>Objectives</h3> To examine the prevalence of clinical and laboratory characteristics of ALPS in a cohort of pediatric patients with cSS in order to better characterize this autoimmune disorder and discover potential novel therapeutic targets. <h3>Methods</h3> Patients with cSS were recruited from the Paediatric Rheumatology Department at the Gaslini Children's Hospital of Genoa, Italy. All consecutive cSS patients underwent clinical and ultrasound assessment to evaluate the presence of signs of lymphoproliferation, such as splenomegaly or lymphadenopathy. The following laboratory examination were performed: complete blood count (CBC), total immunoglobulins and immunoglobulins G (IgG) subclasses, vitamin B12 levels, peripheral blood lymphocyte subsets including double negative T cells (DNTs), interleukin 10 (IL-10), interleukin 18 (IL-18) and soluble FAS ligand (sFASL) levels, a lymphocyte apoptosis test and a Next Generation Sequencing (NGS) panel. <h3>Results</h3> Twenty patients were included in the present study. All but one patient were female (95%) with a median age at disease onset of 9,5 years. 4/20 (20%) had persistent lymphadenopathy and 1/20 (5%) had a splenomegaly. Four patients (20%) had persistent cytopenias and 12/20 (60%) had a hypergammaglobulinemia. Three patients (15%) had a deficit of IgG4 and another one (5%) had a deficit of IgG1 and IgG2. Three patients (15%) fulfilled the Oliveira's criteria for ALPS-like disorders [3] and of these, two had mutations in ALPS-like involved genes (PI3KCD and TNFRSF13B). Two other patients (10%) were diagnosed as ALPS-like disorders based on the presence of at least three out of four screening markers in cytofluorimetric panels (DNTs &gt; 1,5%, TCRαβ B220<sup>+</sup> &gt; 60%, CD3<sup>+</sup>CD25<sup>+</sup>/CD3<sup>+</sup>HLA DR<sup>+</sup> ratio &lt; 1, CD27<sup>+</sup> B cells &lt; 15%) [4]. Overall, 5 out of 20 (25%) cSS patients had an ALPS-like phenotype and started treatment with sirolimus with a good clinical and biochemical response. <h3>Conclusion</h3> This is the first description of an overlapping syndrome between cSS and ALPS. A substantial proportion of cSS patients followed at our Centre fulfilled diagnostic criteria for ALPS-like disorders and were treated successfully with sirolimus, a mammalian target of rapamycin (mTOR) inhibitor. Our results emphasize the need for a broader understanding of the immune dysregulation underlining cSS to identify novel therapeutic targets. <h3>References</h3> [1]Ramos-Casals M, et al. Childhood-onset of primary Sjögren's syndrome: phenotypic characterization at diagnosis of 158 children. Rheumatology (Oxford). 2021 Oct 2;60(10):4558-4567. [2]Marino A, et al. Childhood Sjogren's syndrome: An Italian case series and a literature review-based cohort. Semin Arthritis Rheum. 2021 Aug;51(4):903-910. [3]Palmisani E, et al. Clinical features and therapeutic challenges of cytopenias belonging to alps and alps-related (ARS) phenotype. Br J Haematol. 2019 Mar;184(5):861-864. [4]Oliveira JB, et al. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. Blood. 2010 Oct 7;116(14):e35-40. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.